Absorbable implantable vaso-occlusive member

ABSTRACT

Compositions comprising absorbable implantable vaso-occlusive members are described. Also described are methods of making and using these absorbable vaso-occlusive compositions.

FIELD OF THE INVENTION

Compositions and methods for repair of aneurysms are described. Inparticular, completely or almost completely absorbable vaso-occlusivemembers are disclosed, as are methods of making and using these members.

BACKGROUND

An aneurysm is a dilation of a blood vessel (similar to a balloon) thatposes a risk to health from the potential for rupture, clotting, ordissecting. Rupture of an aneurysm in the brain causes stroke, andrupture of an aneurysm in the abdomen causes shock. Cerebral aneurysmsare usually detected in patients as the result of a seizure orhemorrhage and can result in significant morbidity or mortality.

There are a variety of materials and devices which have been used fortreatment of aneurysms, including platinum and stainless steelmicrocoils, polyvinyl alcohol sponges (Ivalone), and other mechanicaldevices. For example, vaso-occlusion devices are surgical implements orimplants that are placed within the vasculature of the human body,typically via a catheter, either to block the flow of blood through avessel making up that portion of the vasculature through the formationof an embolus or to form such an embolus within an aneurysm stemmingfrom the vessel. One widely used vaso-occlusive device is a helical wirecoil having windings which may be dimensioned to engage the walls of thevessels. (See, e.g., U.S. Pat. No. 4,994,069 to Ritchart et al.) Otherless stiff helically coiled devices have been described, as well asthose involving woven braids.

U.S. Pat. No. 5,354,295 and its parent, U.S. Pat. No. 5,122,136, both toGuglielmi et al., describe an electrolytically detachable embolicdevice. Vaso-occlusive coils having little or no inherent secondaryshape have also been described. For instance, co-owned U.S. Pat. Nos.5,690,666 and 5,826,587 by Berenstein et al., describes coils havinglittle or no shape after introduction into the vascular space.

Attempts to increase thrombogenicity of metal coils have also beenattempted, for example by modifying the surface of the coil. WO 99/44538discloses use of GDC coils coated with biodegradable polymers orproteins. U.S. Pat. No. 5,669,931 to Kupiecki discloses coils that maybe filed or coated with thrombotic or medicinal material. U.S. Pat. No.5,749,894 to Engleson discloses polymer coated vaso-occlusion devices.U.S. Pat. No. 5,690,671 to McGurk discloses an embolic element which mayinclude a coating, such as collagen, on the filament surface. U.S. Pat.No. 5,536,274 to Neuss shows spiral implants, some of which are coatedwith metal particles, silicone, PTFE, rubber latices, or polymers. U.S.Pat. No. 5,980,550 describes a vaso-occlusive device having a bioactiveinner coating and a water-soluble outer coating. Co-owned WO/027445,titled “Bioactive Coating for Vaso-occlusive Devices,” describesvaso-occlusive devices coated with a collagen-based material and,additionally, describes the use of a tie-layer between the device andthe collagen-based coating.

Liquid embolics, such as cyanoacrylate glues and fibrin sealants, havealso been used in animal and human subjects. See, e.g., InterventionalRadiology, Dandlinger et al, ed., Thieme, N.Y., 1990:295-313; Suga etal. (1992) No Shinkei Geka 20(8):865-873; Moringlane et al. (1987) SurgNeurol 28(5):361-366; Moringlane et al. (1988) Acta Neurochir Suppl.(Wein) 43:193-197. Of these liquid embolics, cyanoacrylate glues are theonly liquid embolics currently available to neurosurgeons. However,chronic inflammation is typically seen with cyanoacrylate treatments(Herrera et al. (1999) Neurol Med Chir (Tokyo) 39(2):134-139) and thedegradation product, formaldehyde, is highly toxic to the neighboringtissues. See, Vinters et al (1995) Neuroradiology 27:279-291. Anotherdisadvantage of cyanoacrylate materials is that the polymer will adhereboth to the blood vessel and to the tip of the catheter. Thus physiciansmust retract the catheter immediately after injection of thecyanoacrylate embolic material or risk adhesion of the cyanoacrylate andthe catheter to the vessel.

WO 00/44306 discloses endovascular apparatuses comprising an at leastpartially absorbable polymeric or protein coil and a placement device.

None of these documents describe vaso-occlusive members having thecharacteristics described herein or methods of making such members.

SUMMARY OF THE INVENTION

Thus, this invention includes novel occlusive compositions as well asmethods of using and making these compositions.

In one aspect, the invention includes an absorbable vaso-occlusivemember comprising: (i) an absorbable material; and (ii) one or morestretch-resistant members fixedly attached to at least two locations ofthe absorbable material. Non-limiting examples of suitable absorbablematerials include polyglygolic acid (PGA), poly-glycolic/poly-L-lacticacid co-polymers, polycaprolactone, polyhydroxybutyrate/hydroxyvaleratecopolymers, poly-L-lactide, polydioxanone, polycarbonates,polyanhydrides, collagen, elastin, fibrinogen, fibronectin, vitronectin,laminin, gelatin and combinations thereof.

The vaso-occlusive members described herein can have anythree-dimensional shape, including, for example, J-shaped, straight,cylindrical, spherical, tube-like, and helical coil. In certainembodiments, for example where the vaso-occlusive member is configuredas a helical coil having a plurality of helical winds, a first end, asecond end and lumen between said first and second ends, thestretch-resistant member extends through said lumen of the coil and isattached to said first and second ends. Alternatively, thestretch-resistant member can be threaded through holes, perforations orwinds of the three-dimensional member (e.g., threaded through winds of acoil or through perforations of a tube). Furthermore, in any of thevaso-occlusive members described the stretch-resistant member can beattached to the interior or, alternatively, exterior of the members(e.g., helical coil or tube).

In certain embodiments, the stretch-resistant member is non-absorbable.In other embodiments, the stretch-resistant member is absorbable. Forexample, absorbable stretch-resistant members can be separately addedelements or, alternatively, the stretch-resistant member(s) can beformed by modifying the absorbable material, for example by heating orsoldering selected locations of the absorbable vaso-occlusive member,e.g., by soldering lines on the exterior or interior of a tube-shapedmember or by heating or soldering one or more winds of a helicallyshaped member to connect at least two of said helical winds. In certainaspects, the stretch-resistant member comprises a mono-filament, forexample polypropylene. In other embodiments, the stretch-resistantmember is a multi-filament.

Any of the vaso-occlusive members described herein can further comprisea deployment tip, for example attached to at least one of the first endand second end of the member (e.g., coil or tube shape). The deploymenttip can be, for example, an electrolytically detachable end adapted todetach from a pusher by imposition of a current on said pusher. Further,any of the vaso-occlusive members described herein can further comprisea radio-opaque material (for example powdered tantalum, powderedtungsten, bismuth oxide, and barium sulfate) and/or a bioactivematerial.

In yet another aspect, a method for producing a vaso-occlusive member isdescribed comprising the steps of (i) preparing a generally linearprimary element comprising an absorbable material; (ii) winding saidprimary element onto a mandrel; and (iii) heating said mandrel and saidprimary element to produce said three dimensional member (e.g, a 15minute heating step at approximately 165° C.). The vaso-occlusive membercan have a variety of three-dimensional configurations including, forexample, a helical coil configuration, a conical shape or a spiralshape. Further, any suitable mandrel can be used, for example, astainless steel mandrel.

In yet another aspect, the invention includes a method for producing avaso-occlusive member comprising the steps of preparing a tube-likestructure comprising an absorbable material, for example bymicro-machining.

In any of the methods described herein, the absorbable material can be,for example, polyglygolic acid (PGA), poly-glycolic/poly-L-lactic acidco-polymers, polycaprolactone, polyhydroxybutyrate/hydroxyvaleratecopolymers, poly-L-lactide, polydioxanone, polycarbonates,polyanhydrides, collagen, elastin, fibrinogen, fibronectin, vitronectin,laminin, gelatin and combinations thereof.

Any of the methods described herein can further include the step offixedly attaching one or more stretch-resistant members to two or morelocations on the vaso-occlusive member, for example by knotting, heatingor soldering the stretch-resistant member to the device or by heating,soldering, or plasticizing portions of the device to each other. In anyof these methods, the stretch-resistant member can be either absorbableor non-absorbable. Furthermore, the stretch-resistant member can be amono-filament, for example, polypropylene or a multi-filament.

In any of the methods described herein, the vaso-occlusive member canfurther comprise one or more radio-opaque material, for example,powdered tantalum, powdered tungsten, bismuth oxide, and barium sulfateand/or one or more bioactive materials.

These and other embodiments of the subject invention will readily occurto those of skill in the art in light of the disclosure herein.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 depicts an exemplary absorbable vaso-occlusive member of thepresent invention having a helical configuration.

FIG. 2 depicts an exemplary stretch-resistant and absorbablevaso-occlusive member according to the present invention.

FIG. 3 depicts an electrolytic GDC-type detachment junction.

DESCRIPTION OF THE INVENTION

Occlusive (e.g., embolic) compositions are described. The emboliccompositions include, for example, completely or substantiallyabsorbable vaso-occlusive members. Additional materials may also be usedin these embolic compositions. The compositions described herein finduse in vascular and neurovascular indications and are particularlyuseful in treating aneurysms, for example small-diameter, curved orotherwise difficult to access vasculature, for example cerebralaneurysms. Methods of making and using these vaso-occlusive members alsoan aspects of this invention.

Advantages of the present invention include, but are not limited to, (i)promoting healing of aneurysms using complete (or virtually complete)absorption rather than partial absorption of the embolic material; (ii)reducing or eliminating painful mass effect associated with someaneurysms or use of some vaso-occlusive devices; (iii) encouraginggreater tissue ingrowth in the aneurysm due to the absorbable nature ofthe member, which in turn results in (iv) more stable aneurysms.

All publications, patents and patent applications cited herein, whetherabove or below, are hereby incorporated by reference in their entirety.

It must be noted that, as used in this specification and the appendedclaims, the singular forms “a”, “an”, and “the” include plural referentsunless the content clearly dictates otherwise. Thus, for example,reference to “a filament” includes a mixture of two or more suchfilaments and the like.

In one aspect, the invention includes absorbable material useful inoccluding aneurysms. The term “absorbable” refers to any agent which,over time, is no longer identifiable at the site of application in theform it was injected, for example having been removed via degradation,metabolism, dissolving or any passive or active removal procedure. Itwill be understood that in certain embodiments, not all of the materialis absorbable. Thus, the term includes both complete and substantiallycomplete absorption over a period of time ranging from hours to months.Preferably, 80-100% (or any value therebetween) of the material isabsorbed; even more preferably 90 to 100% (or any value therebetween) ofthe material is absorbed and most preferably 100% of the material isabsorbed over time. Thus, absorbable vaso-occlusive members are to becontrasted with hybrid devices made up of both absorbable material andnon-absorbable material, such as nitinol, in which less thansubstantially all of the device is absorbed over time.

Thus, described herein are novel structures and novel methods ofmanufacturing absorbable vaso-occlusive members. Absorbable materialssuitable for use in the compositions and methods of the presentinvention include, but are not limited to, polymers and proteins.Suitable polymers include, for example, polyglygolic acid (PGA),poly-glycolic/poly-L-lactic acid co-polymers, polycaprolactone,polyhydroxybutyrate/hydroxyvalerate copolymers, poly-L-lactide,polydioxanone, polycarbonates, and polyanhydrides. Non-limiting examplesof bioabsorbable proteins include collagen, elastin, fibrinogen,fibronectin, vitronectin, laminin and gelatin. Many of these materialsare commercially available. Fibrin-containing compositions arecommercially available, for example from Baxter. Collagen containingcompositions are commercially available, for example from CohesionTechnologies, Inc., Palo Alto, Calif. Fibrinogen-containing compositionsare described, for example, in U.S. Pat. Nos. 6,168,788 and 5,290,552.As will be readily apparent, absorbable materials can be used alone orin any combination with each other. The absorbable material may be inthe form of a mono-filament or, alternatively, a multi-filament strands.

Furthermore, the absorbable materials can also be used in combinationwith additional components. For example, lubricious materials (e.g.,hydrophilic) materials may be used to coat the member to help facilitatedelivery. One or more bioactive materials may also be included. The term“bioactive” refers to any agent which exhibits effects in vivo, forexample a thrombotic agent, a therapeutic agent or the like.Non-limiting examples of bioactive materials include cytokines;extracellular matrix molecules (e.g., collagen); trace metals (e.g.,copper); and other molecules that stabilize thrombus formation orinhibit clot lysis (e.g., proteins or functional fragments of proteins,including but not limited to Factor XIII, (α₂-antiplasmin, plasminogenactivator inhibitor-1 (PAI-1) or the like). Non-limiting examples ofcytokines which may be used alone or in combination in the practice ofthe present invention include, basic fibroblast growth factor (bFGF),platelet derived growth factor (PDGF), vascular endothelial growthfactor (VEGF), transforming growth factor beta (TGF-β) and the like.Cytokines, extracellular matrix molecules and thrombus stabilizingmolecules (e.g., Factor XIII, PAI-1, etc.) are commercially availablefrom several vendors such as, for example, Genzyme (Framingham, Mass.),Genentech (South San Francisco, Calif.), Amgen (Thousand Oaks, Calif.),R&D Systems and Immunex (Seattle, Wash.). Additionally, bioactivepolypeptides can be synthesized recombinantly as the sequence of many ofthese molecules are also available, for example, from the GenBankdatabase. Thus, it is intended that the invention include use of DNA orRNA encoding any of the bioactive molecules. Furthermore, it isintended, although not always explicitly stated, that molecules havingsimilar biological activity as wild-type or purified cytokines,extracellular matrix molecules and thrombus-stabilizing proteins (e.g.,recombinantly produced or mutants thereof) and nucleic acid encodingthese molecules are intended to be used within the spirit and scope ofthe invention. Further, the amount and concentration of liquid embolicand/or other bioactive materials useful in the practice of the inventioncan be readily determined by a skilled operator and it will beunderstood that any combination of materials, concentration or dosagecan be used, so long as it is not harmful to the subject.

It also may be desirable to include one or more radio-opaque materialsfor use in visualizing the members in situ. Thus, the absorbable membersmay be coated or mixed with radio-opaque materials such as metals (e.g.tantalum, gold or platinum particles); barium sulfate; bismuthsubcarbonate; or the like.

The absorbable vaso-occlusive members may take on a variety of shapes(e.g., configurations). FIG. 1 shows one embodiment of the presentinvention in which the absorbable material takes on a helical shape upondeployment. Braided absorbable vaso-occlusive members are also includedwithin the scope of the present invention. For example, a multi-leadbraid can be made by braiding absorbable material(s) around a removablecore wire. Additionally, the vaso-occlusive member may take the form ofa tube-like structure, with or without one or more perforations orholes. It is further within the scope of this invention that theabsorbable vaso-occlusive device comprise shapes or structures otherthan coils, braids and tubes, for examples, J-shaped, straight,cylindrical, spheres, ellipses, spirals, figure-8 shapes, etc. Any ofthe vaso-occlusive members described herein, for example tube-likestructures, may be partially or fully micro-machined.

In certain embodiments, the vaso-occlusive members are“stretch-resistant.” (See, e.g., U.S. Pat. Nos. 6,193,728; 6,013,084;6,004,338; 5,853,418; and 5,833,705 for a description of non-absorbablestretch-resistant devices, all of which are hereby incorporated byreference in their entireties). Typically, stretch-resistant devicesinclude a stretch-resistant member fixedly attached to two or morepoints on the device. The stretch-resistant member may be absorbable or,alternatively, may be a substantially non-absorbed material such aspolypropylene. Both absorbable and non-absorbable materials (e.g.,suture materials) are commonly available and can be used in thecompositions and methods described herein.

The stretch-resistant member can be fixed to the absorbable device inone or more locations, for example near the ends, on the inside oroutside surface or combinations thereof. Furthermore, thestretch-resistant member can be attached by any means, including, butnot limited, to heating (e.g. soldering), threading, knotting,plasticizing, etc. Additionally, in certain embodiments, thestretch-resistant member(s) are formed by modifying the absorbablematerial so as to connect selected regions of the vaso-occlusive memberto one another. For example, two or more individual winds of a helicallyshaped absorbable vaso-occlusive device may be heated, soldered orotherwise treated so that they are connected or otherwise fused, therebyforming one or more stretch-resistant members (and a stretch-resistantdevice). Similarly, one or more modified regions may be formed byheating, soldering, plasticizing or the like, selected areas of atube-shaped absorbable structure to make it stretch-resistant. It willbe apparent that the modified regions may be of any shape, for examplelines, curves, etc, and may be parallel or at angles to each otherand/or parallel or at various angles to the longitudinal axis of thetube. Any of the modifications to the absorbable material that renderthe device stretch-resistant may be on the interior and/or exteriorsurfaces of the vaso-occlusive member.

Methods of Manufacture

Methods of making the absorbable vaso-occlusive members described arealso provided. The vaso-occlusive members described herein are typicallyformed by winding the absorbable material into a first helix, typicallya coil; the first helix is then wound into a secondary form. Typically,the secondary form is one which, when ejected from a delivery catheter,forms a three-dimensional shape to substantially fill the body cavity.Desirably, the vaso-occlusive member is of a size and shape suitable forfitting snugly within a vascular cavity (e.g., an aneurysm, or perhaps,a fistula).

Primary and secondary forms are generally provided by shaping theabsorbable material, for example, winding the material on a mandrel or aremovable core wire. Vaso-occlusive members according to the presentinvention can also be formed by winding a single or multi-leadabsorbable material(s) around a removable core wire. Suitable windingmandrels, for winding both primary and secondary configurations, may bea variety of shapes (e.g., cylindrical, square, spherical, circular,rectangular, etc.) and may be solid or hollow. Some exemplary shapes ofmandrels are shown in co-owned U.S. Pat. No. 5,957,948 to Mariant et al.As noted above, the winding mandrel is typically of sufficient heatresistance to allow a moderate annealing step. The mandrel may be madeof stainless steel or other metallic material, alumina, zirconia or thelike. Composite mandrels (e.g., composites of conductive andnon-conductive materials) described in co-owned U.S. Ser. No. 09/637,470may also be employed.

Further, it is usually desirable to ensure that the primary coil doesnot unravel, for example by taping, clipping or otherwise attaching theprimary coil (e.g., the ends) to the mandrel. The primary coil-mandrelcomplex is preferably annealed at a temperature between about 50° and200° C., more preferably between about 75° and 150° C. and even morepreferably around 100° C. The time of annealing can vary from seconds tohours. Annealing may be omitted or performed at different temperatures,so long as the coil retains its shape after winding and can be readilyremoved from the mandrel.

In certain embodiments, the primary configuration is then wound into asecondary configuration on a mandrel. Again, suitable mandrels can beselected by the operator based on the desired size and shape of theresulting vaso-occlusive member. As with procedures for winding theprimary configuration, clips or other securing means (e.g., tape) may beused to secure the vaso-occlusive member to the selected mandrel. Thesecondary coil-mandrel complex is preferably annealed, for example at atemperature between about 100° and 500° C., more preferably betweenabout 100° and 200° C. and even more preferably between about 160 and170° C. The time of annealing can vary from seconds to hours. Theabsorbable material may be wound or braided on the mandrel or othersupport structure manually. Alternatively, winding machines arecommercially available and can be programmed to wind the absorbablematerial as desired. An exemplary helical secondary configuration isshown in FIG. 1.

As noted above, the devices described herein may also assume a varietyof shapes upon deployment. An exemplary helical secondary configurationis shown in FIG. 1. Other shapes include, but are not limited to,spherical, ovoid, Figure-8, conical, spiral, random three-dimensionalshapes and the like.

In certain embodiments, the absorbable device is made byinjection-molding and/or micro-machining. (See, e.g., co-owned U.S.patent application entitled “Injection Molded Vaso-Occlusive Elements,”filed even date herewith).

In embodiments that include a stretch-resistant member, thestretch-resistant member can be attached to the vaso-occlusive member inany number of ways including but not limited to, looping or threading ofthe stretch-resistant member through the turns and/or lumen (if thevaso-occlusive member is of a configuration to permit such looping orthreading); heating, soldering; plasticizing or solvating the junctionpoints to soften the material at the junction and, subsequently allowingre-solidification; or combinations of one or more of these procedures.For example, when the absorbable device is of a helical configuration ora tube with perforations, the stretch-resistant member may be threadedthrough the coil winds or through the perforations. It will also beapparent that the stretch-resistant member may be attached by any ofthese methods to the interior or exterior surface of the device. Asnoted above, the stretch-resistant member may be either absorbable ornon-absorbable. In certain embodiments, the stretch-resistant member(s)are formed from the absorbable material itself, for example, by heatingor plasticizing selected regions of the device to fuse or otherwiseconnect the regions and make the device stretch-resistant. In view ofthe teachings herein, those skilled in the art will be readily able todetermine which regions of the absorbable material should be modifiedand how the connections should be made.

Additional materials (e.g., bioactive materials and/or radio-opaquematerials) can be made included using any conventional techniques, forexample by dipping, coating or soaking the absorbable vaso-occlusivemember in the additional material(s). Other techniques as known in theart, such as shrink-wrapping, spraying may also be used. In additional,the additional material(s) may be injected into the interior lumenand/or exterior surfaces of the absorbable member.

Methods of Use

The embolic compositions described herein are often introduced into aselected site using the procedure outlined below. This procedure may beused in treating a variety of maladies. For instance in the treatment ofan aneurysm, the aneurysm itself will be filled (partially or fully)with the compositions described herein.

Conventional catheter insertion and navigational techniques involvingguidewires or flow-directed devices may be used to access the site witha catheter. The mechanism will be such as to be capable of beingadvanced entirely through the catheter to place absorbablevaso-occlusive member at the target site but yet with a sufficientportion of the distal end of the delivery mechanism protruding from thedistal end of the catheter to enable detachment of the implantablevaso-occlusive member. For use in peripheral or neural surgeries, thedelivery mechanism will normally be about 100-200 cm in length, morenormally 130-180 cm in length. The diameter of the delivery mechanism isusually in the range of 0.25 to about 0.90 mm. Briefly, the liquidembolics and/or occlusive members described herein are typically loadedinto a carrier for introduction into the delivery catheter andintroduced to the chosen site using the procedure outlined below. Thisprocedure may be used in treating a variety of maladies. For instance,in treatment of an aneurysm, the aneurysm itself may be filled with theembolics (e.g., mechanical devices, absorbable vaso-occlusive membersand/or liquid embolics and bioactive materials) which cause formation ofan emboli and, at some later time, is at least partially replaced byneovascularized collagenous material formed around the implantedvaso-occlusive members.

A selected site is reached through the vascular system using acollection of specifically chosen catheters and/or guide wires. It isclear that should the site be in a remote site, e.g., in the brain,methods of reaching this site are somewhat limited. One widely acceptedprocedure is found in U.S. Pat. No. 4,994,069 to Ritchart, et al. Itutilizes a fine endovascular catheter such as is found in U.S. Pat. No.4,739,768, to Engelson. First of all, a large catheter is introducedthrough an entry site in the vasculature. Typically, this would bethrough a femoral artery in the groin. Other entry sites sometimeschosen are found in the neck and are in general well known by physicianswho practice this type of medicine. Once the introducer is in place, aguiding catheter is then used to provide a safe passageway from theentry site to a region near the site to be treated. For instance, intreating a site in the human brain, a guiding catheter would be chosenwhich would extend from the entry site at the femoral artery, up throughthe large arteries extending to the heart, around the heart through theaortic arch, and downstream through one of the arteries extending fromthe upper side of the aorta. A guidewire and neurovascular catheter suchas that described in the Engelson patent are then placed through theguiding catheter. Once the distal end of the catheter is positioned atthe site, often by locating its distal end through the use of radiopaquemarker material and fluoroscopy, the catheter is cleared. For instance,if a guidewire has been used to position the catheter, it is withdrawnfrom the catheter and then the assembly, for example including theabsorbable vaso-occlusive member at the distal end, is advanced throughthe catheter.

Once the selected site has been reached, the absorbable vaso-occlusivemember is extruded, for example by loading onto a pusher wire.Preferably, the vaso-occlusive member is loaded onto the pusher wire viaa mechanically or electrolytically cleavable junction (e.g., a GDC-typejunction that can be severed by application of heat, electrolysis,electrodynamic activation or other means). Additionally, thevaso-occlusive member can be designed to include multiple detachmentpoints, as described in co-owned U.S. patent application titled“LIGHT-ACTIVATED MULTI-POINT DETACHMENT MECHANISM”. They are held inplace by gravity, shape, size, volume, magnetic field or combinationsthereof. As noted above, the order in which the components of thevaso-occlusive composition are released from the catheter is notcritical to the practice of the invention and can be determined by theoperator.

EXAMPLES Example 1 Primary Configuration

We produced a series of primary coils having made from absorbable PGAmaterials from 0.0055″ PGA mono-filament (0.0055″, Biogeneral FiberTechnology, Batch # 2005-154) wound over a 0.007″ OD stainless steelmandrel, with or without PTFE tubing. The primary coils were wound usingthe procedures discussed above and annealed at a temperature of 100° C.for 10 minutes. Well-shaped, easy to remove primary coils were formed.

Example 2 Secondary Configuration

A series of absorbable vaso-occlusive members having secondaryconfigurations were also produced. Primary coils were producedessentially as described in Example 1 and then the primary coil waswound into a secondary configuration, with or without PTFE tubing,around a 0.004″ OD stainless steel mandrel. The secondary shapes wereannealed at a temperature of 165° C. for between about 15 and 30minutes. Absorbable vaso-occlusive members with secondaryconfigurations, such as those shown in the Figures, were formed.

Example 3 Stretch-Resistant Configurations

Absorbable vaso-occlusive members with secondary configurations producedas described in Example 2 were then modified to be stretch-resistant. Inparticular, the coil was modified so that suture material(non-absorbable, polypropylene mono-filament suture) was attached bythreading and/or by soldering at two more locations of the secondaryconfiguration. Subsequently, the suture-containing absorbablevaso-occlusive member was attached to a pusher wire for deployment.

Modifications of the procedure and vaso-occlusive members describedabove, and the methods of using them in keeping with this invention willbe apparent to those having skill in this mechanical and surgical art.These variations are intended to be within the scope of the claims thatfollow.

What is claimed is:
 1. An absorbable vaso-occlusive member comprising:(i) an absorbable material having a three-dimensional configuration; and(ii) one or more absorbable stretch-resistant members fixedly attachedto at least two locations of the absorbable material, wherein thestretch-resistance members are formed from the absorbable material. 2.The vaso-occlusive member of claim 1, wherein the vaso-occlusive memberhas a configuration selected from the group consisting of J-shaped,straight, cylindrical, spherical, tube-like, and helical coil.
 3. Thevaso-occlusive member of claim 2, wherein the absorbable material isconfigured as a helical coil having a plurality of helical winds, afirst end, a second end and lumen between said first and second ends. 4.The vaso-occlusive member of claim 3, wherein the stretch-resistantmember extends through said lumen of the coil and is attached to saidfirst and second ends.
 5. The vaso-occlusive member of claim 3, whereinthe stretch-resistant member is threaded through the winds of said coil.6. The vaso-occlusive member of claim 3, wherein the stretch-resistantmember is attached to the interior or exterior of the helical coil. 7.An absorbable vaso-occlusive member comprising: (i) a tubular absorbablematerial having a plurality of perforations therein; and (ii) one ormore stretch-resistant members fixedly attached to at least twolocations of the absorbable material.
 8. The vaso-occlusive member ofclaim 7, wherein the stretch-resistant member is threaded through atleast two of said perforations.
 9. The vaso-occlusive member of claim 1,wherein the stretch-resistant members are formed by modifying thethree-dimensional absorbable material.
 10. The vaso-occlusive device ofclaim 1, wherein the absorbable material is modified by heating orsoldering at selected locations.
 11. The vaso-occlusive device of claim10, wherein the absorbable material is shaped as a helical coilcomprising a plurality of helical winds and wherein the heating orsoldering serves to connect at least two of said helical winds.
 12. Thevaso-occlusive device of claim 10, wherein the absorbable material isshaped as a tube and wherein the heating or soldering is at one or morepositions on the exterior or interior of the tube.
 13. Thevaso-occlusive member of claim 1, wherein the absorbable material isselected from the group consisting of polyglygolic acid (PGA),poly-glycolic/poly-L-lactic acid copolymers, polycaprolactone,polyhydroxybutyrate/hydroxyvalerate copolymers, poly-L-lactide,polydioxanone, polycarbonates, polyanhydrides, collagen, elastin,fibrinogen, fibronectin, vitronectin, laminin, gelatin and combinationsthereof.
 14. The vaso-occlusive member of claim 1, wherein thestretch-resistant member is a mono-filament.
 15. The vaso-occlusivemember of claim 14, wherein the mono-filament comprises polypropylene.16. The vaso-occlusive member of claim 1, wherein the stretch-resistantmember is a multi-filament.
 17. The vaso-occlusive member of claim 1,further comprising a deployment tip.
 18. The vaso-occlusive member ofclaim 17, wherein the deployment tip comprises an electrolyticallydetachable end adapted to detach from a pusher by imposition of acurrent on said pusher.
 19. The vaso-occlusive member of claim 1,further comprising a radio-opaque material.
 20. The method of claim 19,where the radio-opaque material is selected from the group consisting ofpowdered tantalum, powdered tungsten, bismuth oxide, and barium sulfate.21. The vaso-occlusive member of claim 1, further comprising a bioactivematerial.
 22. A method for producing a vaso-occlusive member comprisingthe steps of preparing a tube-like structure comprising an absorbablematerial, wherein the preparing comprises micro-machining.
 23. Themethod of claim 22, wherein the absorbable material is selected from thegroup consisting of polyglygolic acid (PGA), poly-glycolic/poly-L-lacticacid co-polymers, polycaprolactone, polyhydroxybutyrate/hydroxyvaleratecopolymers, poly-L-lactide, polydioxanone, polycarbonates,polyanhydrides, collagen, elastin, fibrinogen, fibronectin, vitronectin,laminin, gelatin and combinations thereof.
 24. The method of claim 22further comprising the step of connecting two for more locations of thevaso-occlusive member to form one or more stretch-resistant members. 25.The method of claim 24, wherein the connections are formed by heating orsoldering the two or more locations to one another.
 26. The method ofclaim 22 wherein the vaso-occlusive member further comprises at leastone radio-opaque material.
 27. The method of claim 26, wherein theradio-opaque material is selected from the group consisting of powderedtantalum, powdered tungsten, bismuth oxide, and barium sulfate.
 28. Themethod of claim 22, wherein the vaso-occlusive member further comprisesat least one bioactive material.